The Respiratory Viruses Section entered into a CRADA with MedImmune in 2006 to develop live attenuated virus vaccines for respiratory syncytial virus (RSV) subgroups A and B, human parainfluenza viruses types 1, 2, and 3 (HPIV1-3), and human metapneumovirus (HMPV). None of the ongoing studies have been completed, so there are no results to report. Phase 2b proof of principle efficacy studies with a RSV subgroup A vaccine candidate and with a recombinant(r) human (H) vaccine PIV3, designated rHPIV3cp45, have been initiated. A study with an rHPIV1 vaccine candidate has been initiated in seropositive adults. [unreadable] [unreadable] A study has been initiated to explore the bioequivalence of the rHPIV3cp45 and the biologically-derived HPIV3cp45 and to define a dose of vaccine that is safe, infectious, and immunogenic in older and younger HPIV3 naive subjects. These studies are in progress and preliminary results indicate that the two versions of HPIV3cp45 vaccine are comparable.[unreadable] [unreadable] Vaccines lots are being manufactured for (1) additional strains of RSV, (2) a HPIV2 mutant, (3) HMPV wt, and (4) two HMPV mutants. Clinical studies with most of these viruses should be initiated in 2009.[unreadable] [unreadable] LID is also conducting clinical research that is not part of the MedImmune CRADA. These studies are examining the use of the bovine PIV3 (BPIV3) as a vector for other paramyxovirus antigens. The studies are exploring two approaches to vaccine development that are based on the principle that replication of recombinant bovine/human PIV3 viruses should be attenuated in humans due to host range sequence differences in the BPIV3 virus genes that restrict replication in humans. Clinical studies have been initiated with the chimeric recombinant virus that contains the HPIV3 HN and F protective antigens as replacements for the corresponding genes on a bovine BPIV3 backbone. The rB/HPIV3 contains multiple attenuating BPIV3 genes. These studies are not complete so the results cannot be reported. The safety and immunogenicity of these vaccine candidates are being compared to that obtained using the second type of rB/HPIV3 vaccine candidate in which a human gene in a HPIV3 backbone is replaced by the corresponding BPIV3 gene. rHPIV3-NB contains the bovine nucleocapsid gene as a replacement for the human nucleocapsid gene and was found to be attenuated in non-human primates. Studies have been initiated with rHPIV3-NB, which appears incompletely attenuated in seronegative humans. A vaccine lot for rHPIV3-NP is being manufactured to complete this study. Once a vector is identified, it can vector RSV or HMPV antigens, thereby protecting against both PIV3 and a second human pathogen.